Cited by 2,274Cholesterol and Lipid MetabolismDrug Transport and Resistance MechanismsNuclear Receptors and Signaling

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Bile Acids: Natural Ligands for an Orphan Nuclear Receptor

Parks, Derek J., Blanchard, Steven G., Bledsoe, Randy K., Chandra, Gyan, Consler, Thomas G., Kliewer, Steven A., Stimmel, Julie B., Willson, Timothy M., Zavacki, Ann Marie, Moore, David D., Lehmann, Jürgen M.·1999·Science

DOI 10.1126/science.284.5418.1365

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Abstract

Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.

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Background
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Authors: Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., Moore, D. D., & Lehmann, J. M.
Affiliations: Molecular Biochemistry,
Molecular Sciences,
Molecular Endocrinology,
Medicinal Chemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.
Baylor College of Medicine (US)
Corresponding author: Willson, Timothy M.
ORCID: Kliewer, Steven A.
Willson, Timothy M.
Zavacki, Ann Marie
Moore, David D.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1999-05-21
Volume: 284
Issue: 5418
Pages: 1365-1368
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.284.5418.1365
OpenAlex: W2171398834
Cited by: 2,274
References: 3
Citations by year: 2026: 66 · 2025: 72 · 2024: 86 · 2023: 75 · 2022: 103 · 2021: 111 · 2020: 102 · 2019: 105 · 2018: 101 · 2017: 113 · 2016: 80 · 2015: 90 · 2014: 80 · 2013: 83 · 2012: 93
FWCI: 78.42
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5f32dk009793-02)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053366, R01-DK53366, F32 DK09793)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: bile acids, farnesoid X receptor, orphan nuclear receptor, cholesterol homeostasis, chenodeoxycholic acid, lithocholic acid, deoxycholic acid, bile acid conjugates, SRC-1, transcriptional regulation
MeSH terms: Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Carrier Proteins, Cell Line, Chenodeoxycholic Acid, Cholesterol, Deoxycholic Acid, DNA-Binding Proteins, Homeostasis, Humans, Ligands, Lithocholic Acid, Protein Conformation, Recombinant Fusion Proteins, Structure-Activity Relationship, Transcription Factors, Transfection, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Symporters, Organic Anion Transporters, Sodium-Dependent, Mice, Histone Acetyltransferases, Nuclear Receptor Coactivator 1

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Bile Acids: Natural Ligands for an Orphan Nuclear Receptor

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